CN111620918A - 8-beta-D-glucopyranose-4', 7-dihydroxyisoflavone FAM derivative and synthetic method thereof - Google Patents
8-beta-D-glucopyranose-4', 7-dihydroxyisoflavone FAM derivative and synthetic method thereof Download PDFInfo
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- CN111620918A CN111620918A CN202010564395.3A CN202010564395A CN111620918A CN 111620918 A CN111620918 A CN 111620918A CN 202010564395 A CN202010564395 A CN 202010564395A CN 111620918 A CN111620918 A CN 111620918A
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- C—CHEMISTRY; METALLURGY
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- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H17/00—Compounds containing heterocyclic radicals directly attached to hetero atoms of saccharide radicals
- C07H17/04—Heterocyclic radicals containing only oxygen as ring hetero atoms
- C07H17/06—Benzopyran radicals
- C07H17/065—Benzo[b]pyrans
- C07H17/07—Benzo[b]pyran-4-ones
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H1/00—Processes for the preparation of sugar derivatives
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H1/00—Processes for the preparation of sugar derivatives
- C07H1/06—Separation; Purification
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Abstract
The invention relates to the technical field of molecular synthesis, in particular to 8- β -D-glucopyranose-4 ', 7-dihydroxyisoflavone FAM derivatives and a synthesis method thereof, wherein the 8- β -D-glucopyranose-4', 7-dihydroxyisoflavone FAM derivatives have the chemical structural formula:
Description
Technical Field
The invention relates to the technical field of molecular synthesis, in particular to 8-beta-D-glucopyranose-4', 7-dihydroxyisoflavone FAM derivatives and a synthesis method thereof.
Background
The kudzu root has the efficacies of relieving exterior syndrome, bringing down fever, promoting the production of body fluid and quenching thirst, and the related research of the puerarin which is the effective component in the kudzu root attracts a lot of attention in recent years. Puerarin (PUE) is a flavonoid glycoside natural drug monomer with the chemical name of 8-beta-D-glucopyranose-4 ', 7-dihydroxyisoflavone, and is widely applied to the treatment of cardiovascular and cerebrovascular diseases, diabetes and diabetic complications, osteonecrosis, Parkinson's disease, Alzheimer's disease, endometriosis and cancer, and the beneficial effects can be probably due to the wide pharmacological properties such as vasodilation, cardioprotection, neuroprotection, antioxidation, anticancer, anti-inflammatory, pain relieving, bone formation promotion, alcohol intake inhibition and insulin resistance weakening, but the potential molecular mechanism and target point are still unclear. The research on the specific positioning of puerarin in the cell is helpful for the research on the pharmacological action mechanism of puerarin, but the problem of how to realize the visualization of puerarin in the cell is a problem in front of researchers.
The fluorescent molecular imaging technology is an emerging molecular imaging technology which is rapidly developed in recent years, labels specific molecules or cells by using a fluorescent molecular probe with specificity, performs spatial and temporal visual description on normal or abnormal biological processes from the molecular and cellular level, and is a non-invasive functional imaging mode. When a certain specific compound is irradiated with light of one wavelength, molecules or atoms of the compound are excited by the incident light, and electrons undergo energy level transition after energy absorption, and reach an excited singlet state from a ground state. Electrons in the excited state are unstable and emit light longer than the wavelength of the excited light in an extremely short time (nanoseconds), returning excited molecules or atoms to the ground state. The return of an atom or molecule in an excited state to the ground state is accompanied by the emission of light called fluorescence. By detecting the intensity of the generated fluorescence with a certain device, a distribution image of the internal fluorescence optical characteristics (such as concentration, service life, quantum yield, absorption and scattering coefficient of the tissue to the fluorescence) of the tissue can be obtained.
The fluorescent molecular imaging technology has the advantages of low cost, simplicity, easy implementation, no ionizing radiation to organisms and the like, and plays an increasingly important role in disease observation, medicine, biology and other researches in living bodies. Molecular imaging is a new subject developed in recent years on the basis of existing medical imaging techniques, and broadly refers to in vivo imaging of organisms at the cellular and molecular levels. The conventional medical imaging technology is a diagnostic imaging that uses physical or physiological characteristics of a living body as an imaging source. In optical molecular imaging, fluorescent molecular imaging utilizes specific fluorescent molecular probes to label specific molecules or cells, with spatial resolution up to mm, which are fluorescent markers that have been used extensively in biological and medical research, well known to life scientists, in vitro imaging. The fluorescent molecular imaging technology promotes the research of drugs, and the development of drugs by means of the fluorescent molecular imaging technology has many advantages compared with the traditional method. Firstly, the time-consuming anatomy and tissue analysis process is saved, and the drug screening process is accelerated; secondly, the method can perform repeated experiments on the same animal, so that the number of experimental animals is reduced, longitudinal research is facilitated, and statistical relevance is improved; finally, the fluorescence molecular imaging technology is used for developing the medicine, so that important information such as medicine dosage, time and the like can be provided in the experimental process. The development of new fluorescent dyes and the improvement of imaging techniques will bring breakthrough progress to the field of pharmaceutical research. No reports related to 8-beta-D-glucopyranose-4', 7-dihydroxyisoflavone FAM derivatives and a synthetic method thereof are found in the prior art.
Disclosure of Invention
In view of the problems of the prior art, the present invention aims to provide a FAM derivative and a synthesis method thereof. The invention utilizes molecular synthesis technology, uses 5-carboxyfluorescein succinimidyl ester (5-FAM-NHS) to modify 8-beta-D-glucopyranose-4 ', 7-dihydroxyisoflavone, connects the 8-beta-D-glucopyranose-4', 7-dihydroxyisoflavone and 5-FAM with stable fluorescence property together, is used for the visual research in puerarin cells and tissues, and brings breakthrough progress to the research field of puerarin pharmacy.
In order to achieve the above object, the present invention adopts the following technical solutions.
An 8-beta-D-glucopyranose-4', 7-dihydroxyisoflavone FAM derivative has a chemical structural formula as follows:
the synthesis method of the 8-beta-D-glucopyranose-4', 7-dihydroxyisoflavone FAM derivative specifically comprises the following steps.
Step 1, dissolving 5-carboxyfluorescein succinimide ester and 8-beta-D-glucopyranose-4', 7-dihydroxyisoflavone in DMSO, adding triethylamine, reacting at room temperature for 12h, and freeze-drying to obtain a crude product.
And 2, separating and purifying the crude product obtained in the step 1 by using a silica gel preparation plate, and drying the eluent in vacuum for 12 hours to obtain yellow powder.
Further, the molar ratio of the 5-carboxyfluorescein succinimidyl ester, the 8-beta-D-glucopyranose-4', 7-dihydroxyisoflavone and the triethylamine in the step 1 is 1:1: 3.
Further, the developing agent in the separation of the glue preparation plate in the step 2: the volume ratio of the dichloromethane to the methanol is 1: 1.
compared with the prior art, the invention has the following beneficial effects.
1) The synthesis method of the 8-beta-D-glucopyranose-4', 7-dihydroxyisoflavone FAM derivative provided by the invention is simple, low in cost and easy for mass production.
2) The 8-beta-D-glucopyranose-4', 7-dihydroxyisoflavone and 5-FAM with stable fluorescence are connected together, so that the method is used for the visual research in puerarin cells and tissues and brings breakthrough progress to the field of puerarin pharmaceutical research.
Detailed Description
The present invention will be further illustrated with reference to the following examples, but the present invention is not limited to the following examples.
Example 18 preparation and characterization of β -D-glucopyranose-4', 7-dihydroxyisoflavone FAM derivatives.
1. A preparation method.
5-FAM-NHS (4.2mg, 10. mu.M), 8-beta-D-glucopyranose-4', 7-dihydroxyisoflavone (4.8 mg, 10. mu.M) were dissolved in 1mL of DMSO, triethylamine (3mg, 30. mu.M) was added, reaction was carried out at room temperature for 12 hours, and freeze-drying was carried out to obtain a crude product, which was isolated and purified using a silica gel preparation plate with a developing solvent of dichloromethane: methanol (volume ratio) 1:1, the eluate was dried in vacuo for 12h to give 7.2mg of yellow powder in 92.8% yield.
2. And (5) analyzing the results of mass spectrometry and nuclear magnetic resonance hydrogen spectroscopy.
MS(ESI)：m/z 775([M-H]+)；1H NMR(400MHz,CDCl3)8.47(s,1H),8.07(s,1H),8.02(s,1H),7.75(d,J＝8.0Hz,1H),7.51(t,J＝8.4Hz,1H),7.40(d,J＝7.6Hz,1H),7.36(d,J＝ 8.8Hz,1H),7.22(d,J＝8.0Hz,1H),7.03(t,J＝8.0Hz,1H),6.80-6.76(m,2H),6.68-6.63(m,1H), 6.49(t,J＝7.6Hz,1H),6.46-6.32(m,1H),6.06(d,J＝7.6Hz,2H),6.03-5.99(m,3H),5.77(d,J＝ 6.8Hz,1H),5.37-5.23(m,2H),5.12(d,J＝6.8Hz,1H),4.66(d,J＝7.2Hz,1H),4.12(t,J＝6.4 Hz,1H),3.80(d,J＝7.2Hz,1H),3.63-3.58(m,2H),3.53-3.46(m,2H),3.34-3.28(m,3H)。
From the above data, it is known that 5-FAM and 8- β -D-glucopyranose-4', 7-dihydroxyisoflavone were successfully linked.
Claims (4)
1. An 8- β -D-glucopyranose-4', 7-dihydroxyisoflavone FAM derivative, which is characterized by having a chemical structural formula as follows:
。
2. the method for synthesizing 8- β -D-glucopyranose-4', 7-dihydroxyisoflavone FAM derivatives according to claim 1, comprising the steps of:
step 1, dissolving 5-carboxyfluorescein succinimide ester and 8-beta-D-glucopyranose-4', 7-dihydroxyisoflavone into DMSO, adding triethylamine, reacting at room temperature for 12h, and freeze-drying to obtain a crude product;
and 2, separating and purifying the crude product obtained in the step 1 by using a silica gel preparation plate, and drying the eluent in vacuum for 12 hours to obtain yellow powder.
3. The method for synthesizing 8- β -D-glucopyranose-4 ', 7-dihydroxyisoflavone FAM derivatives according to claim 2, wherein the molar ratio of 5-carboxyfluorescein succinimidyl ester, 8- β -D-glucopyranose-4', 7-dihydroxyisoflavone to triethylamine in step 1 is 1:1: 3.
4. a method of synthesizing 8- β -D-glucopyranose-4', 7-dihydroxyisoflavone FAM derivatives according to claim 2, wherein the gel preparation plate in step 2 is subjected to a developing solvent in the separation: the volume ratio of the dichloromethane to the methanol is 1: 1.
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